Transcriptional upregulation of p19INK4d upon diverse genotoxic stress is critical for optimal DNA damage response
p19INK4d promotes survival of several cell lines after UV irradiation due to enhanced DNA repair, independently of CDK4 inhibition. To further understand the action of p19INK4d in the cellular response to DNA damage, we aimed to elucidate whether this novel regulator plays a role only in mechanisms...
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2009
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13572725_v41_n6_p1344_Ceruti http://hdl.handle.net/20.500.12110/paper_13572725_v41_n6_p1344_Ceruti |
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paper:paper_13572725_v41_n6_p1344_Ceruti2023-06-08T16:11:19Z Transcriptional upregulation of p19INK4d upon diverse genotoxic stress is critical for optimal DNA damage response Ceruti, Julieta María Scassa, María Elida Marazita, Mariela C. Carcagno, Abel Luis Cánepa, Eduardo Tomás Apoptosis Cell survival DNA damage Genotoxic stress INK4 amyloid beta protein cisplatin cyclin dependent kinase inhibitor 2D messenger RNA animal cell apoptosis article cell cycle arrest cell damage cell survival clonogenesis controlled study DNA damage DNA repair DNA structure enzyme induction gene expression genetic transfection genotoxicity molecular mechanics neuroblastoma cell nonhuman protein expression protein synthesis RNA stability transcription initiation ultraviolet radiation upregulation Amyloid beta-Protein Animals Apoptosis Blotting, Northern Cell Line Cell Survival Cisplatin Cricetinae Cyclin-Dependent Kinase Inhibitor p19 DNA Damage DNA Repair Humans Neuroblastoma RNA, Messenger Transcriptional Activation Transfection Tumor Suppressor Protein p53 Ultraviolet Rays Up-Regulation p19INK4d promotes survival of several cell lines after UV irradiation due to enhanced DNA repair, independently of CDK4 inhibition. To further understand the action of p19INK4d in the cellular response to DNA damage, we aimed to elucidate whether this novel regulator plays a role only in mechanisms triggered by UV or participates in diverse mechanisms initiated by different genotoxics. We found that p19INK4d is induced in cells injured with cisplatin or β-amyloid peptide as robustly as with UV. The mentioned genotoxics transcriptionally activate p19INK4d expression as demonstrated by run-on assay without influencing its mRNA stability and with partial requirement of protein synthesis. It is not currently known whether DNA damage-inducible genes are turned on by the DNA damage itself or by the consequences of that damage. Experiments carried out in cells transfected with distinct damaged DNA structures revealed that the damage itself is not responsible for the observed up-regulation. It is also not known whether the increased expression of DNA-damage-inducible genes is related to immediate protective responses such as DNA repair or to more delayed responses such as cell cycle arrest or apoptosis. We found that ectopic expression of p19INK4d improves DNA repair ability and protects neuroblastoma cells from apoptosis caused by cisplatin or β-amyloid peptide. Using clonal cell lines where p19INK4d levels can be modified at will, we show that p19INK4d expression correlates with increased survival and clonogenicity. The results presented here, prompted us to suggest that p19INK4d displays an important role in an early stage of cellular DNA damage response. © 2008 Elsevier Ltd. All rights reserved. Fil:Ceruti, J.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Scassa, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Marazita, M.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Carcagno, A.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Cánepa, E.T. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2009 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13572725_v41_n6_p1344_Ceruti http://hdl.handle.net/20.500.12110/paper_13572725_v41_n6_p1344_Ceruti |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Apoptosis Cell survival DNA damage Genotoxic stress INK4 amyloid beta protein cisplatin cyclin dependent kinase inhibitor 2D messenger RNA animal cell apoptosis article cell cycle arrest cell damage cell survival clonogenesis controlled study DNA damage DNA repair DNA structure enzyme induction gene expression genetic transfection genotoxicity molecular mechanics neuroblastoma cell nonhuman protein expression protein synthesis RNA stability transcription initiation ultraviolet radiation upregulation Amyloid beta-Protein Animals Apoptosis Blotting, Northern Cell Line Cell Survival Cisplatin Cricetinae Cyclin-Dependent Kinase Inhibitor p19 DNA Damage DNA Repair Humans Neuroblastoma RNA, Messenger Transcriptional Activation Transfection Tumor Suppressor Protein p53 Ultraviolet Rays Up-Regulation |
| spellingShingle |
Apoptosis Cell survival DNA damage Genotoxic stress INK4 amyloid beta protein cisplatin cyclin dependent kinase inhibitor 2D messenger RNA animal cell apoptosis article cell cycle arrest cell damage cell survival clonogenesis controlled study DNA damage DNA repair DNA structure enzyme induction gene expression genetic transfection genotoxicity molecular mechanics neuroblastoma cell nonhuman protein expression protein synthesis RNA stability transcription initiation ultraviolet radiation upregulation Amyloid beta-Protein Animals Apoptosis Blotting, Northern Cell Line Cell Survival Cisplatin Cricetinae Cyclin-Dependent Kinase Inhibitor p19 DNA Damage DNA Repair Humans Neuroblastoma RNA, Messenger Transcriptional Activation Transfection Tumor Suppressor Protein p53 Ultraviolet Rays Up-Regulation Ceruti, Julieta María Scassa, María Elida Marazita, Mariela C. Carcagno, Abel Luis Cánepa, Eduardo Tomás Transcriptional upregulation of p19INK4d upon diverse genotoxic stress is critical for optimal DNA damage response |
| topic_facet |
Apoptosis Cell survival DNA damage Genotoxic stress INK4 amyloid beta protein cisplatin cyclin dependent kinase inhibitor 2D messenger RNA animal cell apoptosis article cell cycle arrest cell damage cell survival clonogenesis controlled study DNA damage DNA repair DNA structure enzyme induction gene expression genetic transfection genotoxicity molecular mechanics neuroblastoma cell nonhuman protein expression protein synthesis RNA stability transcription initiation ultraviolet radiation upregulation Amyloid beta-Protein Animals Apoptosis Blotting, Northern Cell Line Cell Survival Cisplatin Cricetinae Cyclin-Dependent Kinase Inhibitor p19 DNA Damage DNA Repair Humans Neuroblastoma RNA, Messenger Transcriptional Activation Transfection Tumor Suppressor Protein p53 Ultraviolet Rays Up-Regulation |
| description |
p19INK4d promotes survival of several cell lines after UV irradiation due to enhanced DNA repair, independently of CDK4 inhibition. To further understand the action of p19INK4d in the cellular response to DNA damage, we aimed to elucidate whether this novel regulator plays a role only in mechanisms triggered by UV or participates in diverse mechanisms initiated by different genotoxics. We found that p19INK4d is induced in cells injured with cisplatin or β-amyloid peptide as robustly as with UV. The mentioned genotoxics transcriptionally activate p19INK4d expression as demonstrated by run-on assay without influencing its mRNA stability and with partial requirement of protein synthesis. It is not currently known whether DNA damage-inducible genes are turned on by the DNA damage itself or by the consequences of that damage. Experiments carried out in cells transfected with distinct damaged DNA structures revealed that the damage itself is not responsible for the observed up-regulation. It is also not known whether the increased expression of DNA-damage-inducible genes is related to immediate protective responses such as DNA repair or to more delayed responses such as cell cycle arrest or apoptosis. We found that ectopic expression of p19INK4d improves DNA repair ability and protects neuroblastoma cells from apoptosis caused by cisplatin or β-amyloid peptide. Using clonal cell lines where p19INK4d levels can be modified at will, we show that p19INK4d expression correlates with increased survival and clonogenicity. The results presented here, prompted us to suggest that p19INK4d displays an important role in an early stage of cellular DNA damage response. © 2008 Elsevier Ltd. All rights reserved. |
| author |
Ceruti, Julieta María Scassa, María Elida Marazita, Mariela C. Carcagno, Abel Luis Cánepa, Eduardo Tomás |
| author_facet |
Ceruti, Julieta María Scassa, María Elida Marazita, Mariela C. Carcagno, Abel Luis Cánepa, Eduardo Tomás |
| author_sort |
Ceruti, Julieta María |
| title |
Transcriptional upregulation of p19INK4d upon diverse genotoxic stress is critical for optimal DNA damage response |
| title_short |
Transcriptional upregulation of p19INK4d upon diverse genotoxic stress is critical for optimal DNA damage response |
| title_full |
Transcriptional upregulation of p19INK4d upon diverse genotoxic stress is critical for optimal DNA damage response |
| title_fullStr |
Transcriptional upregulation of p19INK4d upon diverse genotoxic stress is critical for optimal DNA damage response |
| title_full_unstemmed |
Transcriptional upregulation of p19INK4d upon diverse genotoxic stress is critical for optimal DNA damage response |
| title_sort |
transcriptional upregulation of p19ink4d upon diverse genotoxic stress is critical for optimal dna damage response |
| publishDate |
2009 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13572725_v41_n6_p1344_Ceruti http://hdl.handle.net/20.500.12110/paper_13572725_v41_n6_p1344_Ceruti |
| work_keys_str_mv |
AT cerutijulietamaria transcriptionalupregulationofp19ink4dupondiversegenotoxicstressiscriticalforoptimaldnadamageresponse AT scassamariaelida transcriptionalupregulationofp19ink4dupondiversegenotoxicstressiscriticalforoptimaldnadamageresponse AT marazitamarielac transcriptionalupregulationofp19ink4dupondiversegenotoxicstressiscriticalforoptimaldnadamageresponse AT carcagnoabelluis transcriptionalupregulationofp19ink4dupondiversegenotoxicstressiscriticalforoptimaldnadamageresponse AT canepaeduardotomas transcriptionalupregulationofp19ink4dupondiversegenotoxicstressiscriticalforoptimaldnadamageresponse |
| _version_ |
1768543960165253120 |